Increased expression of TGF- beta 1 reduces tumor growth of human U-87 Glioblastoma Cells in vivo

The role that transforming growth factor beta 1 (TGF- beta 1) plays in influencing growth of glioma cells is somewhat controversial. To further understand the potential growth-regulatory effects of TGF- beta 1,we constructed an animal astroglial tumor model by injecting either wild-type or virally transduced human U-87 glioblastoma cells into nude rat brains. Wild type U-87 cells produced very low amounts of TGF- beta 1 and were highly tumorigenic. In contrast, U-87 cells transduced to express high levels of TGF- beta 1 showed reduced tumor size in vivo, in a dose-dependent manner. This reduction in tumor size was not due to either decreased vascularity or increased apoptosis. To test whether TGF- beta 1 overproduction inhibited tumor growth through an autocrine mechanism, the highest TGF- beta 1 producing cells were then double transduced with a vector expressing the kinase-truncated type II TGF- beta receptor. Cells expressing high levels of truncated TGF- beta receptor were less sensitive to TGF- beta 1 mediated growth inhibition in vitro and produced more aggressive tumors in vivo. The data suggest that the degree of tumorigenicity of the U-87 high-grade glioblastoma cell line may be associated with correspondingly low level of production of TGF- beta 1. These results also would tend to support the possibility that TGF- beta 1 may be useful in treating some high-grade gliomas.